neem-based natural product innovations: analysis of...
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Journal of Intellectual Property Rights Vol 6 January 2001 pp 27-37
Neem-based Natural Product Innovations: Analysis of Patents
M M S Karki
Nationallllstitute of Science Communication Dr K S Krishnan Road, New Delhi 110012
(Receivcd 4 Deccmber 20 00)
In the recent past, a number of patents have been fil ed on propelties, chemical composition, and active principles of neem tree. In this paper, patent analysis of neem-related patents has been underutken. It aims at identifying the current status of research effOlts and potential commercial uses of various neem products. Between 1985 and 2000, more than 60 patents have been granted all over the world on the neem-based innovations, and most of them are on the pesticidal property. Patents dealing with new extracts , compounds, products or uses are more than patents on new manufacturing processes. Analysis indicates constant efforts towards improvement in the purity of the extract of the active ingredients. Another challenge appears to be how to increase the s torage stability of azadirachtin, which is essential for enhancing its shelf-life and marketability The industrial firms of USA have sizable number of US neem-related patents. In India, CSIR has played an active role in obtaining neem patents.
N eem tree (Azadirachta indica) is an evergreen of th e tropics and sub-tropics related to mahogany. Native to east India and Burma, it grows in much of Southeast Asia and west Africa.1,2Indians have known the medicinal properties of neem since time immemorial. Th e earliest Sanskrit medicinal writings refer to the benefits of neem fruits, seeds, oil, leaves, roots and barks. Each of these has been used in the Ayurvedic and
Unani systems of medicine and provides an answer to many incurable diseases. Traditionally, neem products have been used against heat rashes, boils, wounds, jaundice, leprosy, skin disorders, stomach ulcers, chickenpox, etc. Today, th e best-established and most widely recognized uses are based on its merits as a general antiseptic. Modern research also confirms neem's curative powers and provides indications that neem
28 J INTELLEC PROP RJGHTS, JANUARY 2001
might, in future, be used much more widely.3,4
In the light of above facts, scientists have turned their attention to this wonder tree and are studying the chemical composition of extracts from leaves, seed kern el, bark and other parts. Their research efforts involve identification, extraction, and isolation of active constituents. Currently, nee m seems to have vast busin ess potential. Tremendous international interest in it can be gauged by the number of patents being filed on various properties, chemical composition, and active principles of this plant. The g rowing innovative and commercial activity in the neem-related products underscores th e need to focus on research efforts and technology trends in this area .
The research on neem oil and neem cake began in the 1920s at the Indian Institute of Science in Bangalore. In 1942, a scientist of the Council of Scientific and Industrial Research (CSIR) isolated nimbin, a biologically active compound, from neem. But Indian scientists failed to take their work forward to the stage of industrial or commercial production. Various laboratories, including the Indian Agricultural Research Institute, New Delhi, have been publishing papers for a long time on the important qualities of the neem as a pesticide, as a nitrification inhibitor to prevent th e loss of applied fertilizers
d '1' S an as a SOl Improver .
In a landmark discovery in th e late 1970s, researchers at the University of Keele, UK, isolated azadirachtin, the key active ingred ient of neem that most current patents focus on. Another country that was showing interestin neem at this time was Germany, which had organized the first international neem conference in 1980. But ultimately, it fell to the lot of US corporations to undertake sus-
tained research on neem for developing a commercial market for it as a pesticid eS.
In this paper, these research efforts have been examined by undertaking an ana lysis of neem patents. Since the traditional and modern uses of various parts of neem tree and its chemical composition, and prevailing commercial activity in neem-related products and processes have a direct bearing on innovative activity, all th ese issues ar e touched upon in this paper before analysing the patenting activity.
The multitude of pesticidal ingredients present in neem account for its pesticidal, insect repellant and other properties. Its ma in chemicals are a mixture of three or [our related compounds, 20 odd compou nd ~; are minor but nonetheless active constituen ts in one way or the other. These compounds main ly belong to a general class of natural prod ucts called "b-iterpenes", more specifically, "limonoids." So far, at least niLe limonoids from neem have demonstrated ability to block insect growth, affecting a range of species that includes some of the most deadly pests of agriculture and human health . New limonoids are sti ll being discovered fro m neem, bu t azadirachtin, salan in , meliantriol and nimbin are the best known and, for now at least, seem to be the most significant compounds. Azadirachtin, one of the first active ingredi ents isolated from neem, has proved to be the tree's main agent for battling insects. It accoun ts for some 90 % of the pesticidal effects of the plant3.
The major use of neem oil is in the soap industry. Soaps and shampoos prepJ red from neem oil control ticks and fl eas wh il e an Ayurvedic neem shampoo is used for greasy scalp. An Ayurvedic prickly h eat powder is also made from it. A neem face pack is prepared for oily and pimple-prone skin. Tooth powder and toothpaste prepared from
KARKI : NEEM-I3ASED NATURAL PRODUCT ... ... . 29
neem are effective dentifrices. Extracts of neem bark, 'Silvose T and 'Silvose TRS: are used as toothpaste and mouth wash, respec-. I 2 tlve y .
A large number of medicines manufactured from neem have come up in the form of ointments, tablets or injections, etc. An ointment is prepared from neem for dermatological use; another neem cream is an excellent fly and mosquito repellent. Researchers at the Defence Institute of Physiology and the National Institute of Immunology, both in New Delhi, have formulated a couple of contraceptives that are undergoing clinical trials. Tablets and injections are also being formulated for chronic malaria2. 6.
Neemrich I and Neemrich II developed by the National Chemical Laboratory, Pune, from neem seed act as repellent against the potato tuber moth. The Indian Institute of Chemical Technology, Hyderabad, has developed Vepacide, a highly antifeedant and insect growth regulator from neem2.
The world's first commercial facility built specially for neem tree-based pesticide manufacture commenced operation in Tumkur, Karnataka, in 1993. The plant was set up as a joint venture by W R Grace & Co of USA and the Indian firm P J Margo Pvt Ltd . It is marketed under the trade names 'Margosan-o', and 'BioNeem'. A neem-based insecticide, Margosan-o is already available in the markets in USA6.
Three new neem-based products- Azatin, Turplex. and Align-have entered the US insecticide market. Two related neem formulations, BioNeem for the consumer market and 'Benefit' for lawn and tllli care, are also available in US markets:~ ..
Neem also provides many useful and valuable commonplace materials. For instance,
oil extracted from the seeds goes into soaps,
waxes, and lubricants, as well as into fuels
for lighting and heating. The solid residue,
left after the oil is extracted from the kernels,
is employed as a fertilizer, animal feed and
soil amendment. In addition, neem wood is
valued for construction, cabinetry, and fuel. The tree bark is tapped for gum and ex
tracted for tannins and dental-care products~.
Of all these products, the oil is perhaps the
most commercially important product. This
mainly finds use in lamps, soaps, and other
non edible products3. Colourless, odourless
and nonbitter edible oil has been extracted
from neem oil by removing sulphur com
pounds that cause bitterness. A two-stage process to extract both azadirachtin and ed
ible oil from the crude neem oil has been
developed at the Central Food Technological Research Institute, Mysore2.
Data and Methodology
Data on Indian patents on neem-related products and processes were collected from
one of the issues of this journal7 as weJl as
from Web site of the Neem Foundation4. For
th e US patents the bibliographic search was made through US patent databaseS with key
words: Neem, neem oil. azadirachtin, and Azadirachta indica.
The keywords in the titles of the patents were used to identify the emerging techno
logical trends. The absb'act and the first page of each of the patent were examined to obtain insights into the inventive activity and
the ownership of the patents.
30 J INTELLEC PROP RlGHTS, JANUARY 2001
Patenting Activity
Indian Patents
This analysis is restricted to the 11 Indian patents given in the Table 1. These pertain mainly to the methods of extraction and isolation of neem oil or to active ingredients or their derivatives. For example, processes have been patented for: (i) isolation of nimbatiktam or nimbidin from neem oil, (ij) isolation of new triterpene d e rivatives of azadirachtin from the neem tree, or (iii) isolation of active, bitter and odoriferous constituents from n ee m seeds. Similarl y , patents have been granted for nee m-based pestic id es, insecticid es or formulations. These includ e: (j) a process fo r the prepara-
tion of neem oil fatty acid distillation based pesticLdes, and (ij) a process for the preparation of insecticidally active composition containing lipids from the neem plant. Anoth er category of patents granted is upgradation of neem oil and other neem products. These patents are for: (i) treatment of neem oil, and (ii) a process for treating (upg rading) neem oil having high free fatty acid content.
In India, neem pate nting activity started as early as in 1979 with the filing of a pate nt application by CSIR for isolation of active principles from neem oil. CSIR and the Hindustan Lever Ltd, Bombay, are the active players so far as Indian patents are co ncerned. CSIR has taken fOllr patents which include: (i) process for th e iso lation fro m
Table I-Indian patents <on neem
153415 Process for the isolation from neem oil of active principle evincing oviposition deterre nt activity in insects
171129 Treatment of neem oil
171888 A process for treating (upgrading) neem oil
171899 A process for treating (upgrading) neem oil having high free fatty acid content
172150 A process for the preparation of neem oil fatty acid distillation residu e based pesticides
173327 A process for extraction of neem oil
173328 A process for isolation of active
173559 A process for isolation of a nimbatiktam or nimbidin from neem oil
173996 A process for the preparation of an active composition containing triterpenes including azadirachtin and its derivatives possessing insect antifeedant and growth inhibitory activity from parts of the neem plants
173997 A process for the preparation of insecticidally active composition containing lipids from the neem plants
173998 A process for the isolation of new triterpene derivatives of azadirachtin from th e parts of neem tree
KARKI : NEEM-BASED NATURAL PRODUCT .... .. . 31
neem oil of active principles evincing oviposition deterrent activity in insects, (ii) process for preparation of an active composition containing triterpenes, (iii) process for the preparation of insecticidally active composition, and (iv) process for the isolation of new tri terpene derivatives of azadirachtin. Hindustan Lever has obtained all the three patents on the processes for upgrading neem oil. Godrej Soaps Ltd, Bombay, has been granted one patent for the preparation of neem oil fatty acid distillation residue based pesticides. The Central Council for Research in Ayurveda and Siddha, New Delhi, has obtained a patent on a process for isolation of nimbatiktam or nimbidin from neem oil. In addition, two patents have bee n granted to on e individual inventor, R Gupta, on e for a process for extraction of neem oil, and another on a process for isolation of active bitter and odoriferous constituents from neem seeds.
Besides th e above-mentioned Indian patents, the Web site of the Neem Foundation4
has described eight more neem-related patent applications, which are listed in Annexure 1. Of th ese, Rohm and Haas Co , Philedelphia, has fil ed four patent applications for: (i) preparation of edible neem oil, (ii) stable extract from neem oil, (iii) preparation of neem seed extract, and (iv) a method for producing azadirachtin.
US Patents
The search for neem-related patents, having keywords neem or azadirachtin or Azadirachta indica or neem oil, in the titles of the patent documents, accounted for 46 patents in US patent database during 1976- 2000 (up to 310ctober 2000). There could be a few more neem patents other than those keywords in their titles mentioned above. No pate nts w e r e granted during 1976-
Table 2-US Patents on neem-related processes and products during 1990-2000
Year No of patents
1990 3
1991 3
1992 2
1993 1
1994 10
1995 8
1996 3
1997 7
1998 4 1999-2000 2
80whereas only three patents were granted during 1980-85. In fact, all the three patents were granted in 1985. Vikwood Ltd, Wisconsin, obtained the firs t patent for a stable anti-pest neem-seed extract. From 1986 to 1989, no neem patent was granted. The patenting rate built up to a crescendo by 1994, with some 10 patents in that year alone. During 1991-95, the number of neem patents rose to 24, rests of the patents were granted during 1996-2000. Year-wise distribution of these patents during 1990-2000 is shown in Table 2. Alist of US patents granted on neem -related processes or products are given in Annexure 2.
Ownership of US Patents
When the 46 patents were classified by the country of the agency which has been assign ed the patents, 30 of them were found to have been held by USA, 12 by India and two each by Japan and Germany.
Companies played a predominant role in accelerating the pace of technological development in this area, as out of a total of 46 patents, 33 patents were held by them. Of
32 J INTELLEC PI<OP RIGHTS, JANUARY 2001
th ese, as many as 27 were helel by US corporation s. On e company that clearly looms large is W R Grace with 13 patents. Other major contributing companies from USA are: Rhohm & Haas Co, Philadelphia, with five patents, FMC Corporation, Philadelphia, and AgriDyn e Technologies, Inc, Utah, having two patents each.
The japanese company, Terumo Corporation, has obtained two patents whereas German company, Trifolio-M GmbH, has taken on e patent. Indian companies holding US patents in neem-related products are: Fortun e Biotech Ltd, Secundrabad, God eraj Soaps Ltd, Bombay, and Tata Oil MiIls, Bombay, with one patent each.
Th e Terumo Corporation, japan, received two patents in 1985, but later japanese researchers do not seem to have followed up with any further work. Germany also demonstrated an early interest in neem; the Max Planck Gesselschaft received a patent in 1990. Since then, Trifolio-M GmbH has received another patent in 1997. The German interest, too, appears to have sporadic and spotty. The US corporations have, however, shown a consistent interest, with a few patents appearing evely year during the 1990s, except in 1994 and 1995 when as many as eight and seven patents were obtained by them respectively. The three leading US corporations in the neem patenting business are W R Grace & Co, Agridyne Technologies Inc and Rohm and Haas Co.
India emerged as a late entrant in neem patenting in USA - the first Indian patent having been obtained by Goderej Soaps Ltd in 1994, the second by CSIR in early 1995, and the third by the National Institute of Immunology in 1996. In the same year Tata Oil Mills Co has also obtained one patent. In 1997, CSIR has taken two patents, and in1998 four patents were taken by various
Indian agencies. In 1999-200 again this number has come down to two.
With corporations holding more than lhreefou rths of all th e patents on neem-related products, research institutions are at a di stan t second place with 12 patents. India is leading in this group of patentees with nin e patents (CSIR is holding seven patents, Dalmia Centre for Biotechnology, and National Institute of Immunology are hold ing one patent each). Max Planck Gesselschaft, Germany, and Native Plant Institute, USA, hold two patents each. There is also one indivi.dual patentee.
Technology Trends
Although classifying patents according to the type of invention is a difficult proposition, three b oad categories can be delineated: (i) application-based invention s, (ii) production/preparation and processes, and (iii) extraction and isolation me thods. A few patents may fall in more than one category.
(a) Application-based Inventions
In this category patents are on products, derivatives, formulations, concentrates, etc having some specific applications. There are 29 patents in this group during the period under review.For example: (i) neem oil as a ma le contraceptive, (ii) stable anti-pes t neem seed extract, (iii) triterpene derivativ es nf azadirachtin having insect a ntifeedant and growth inhibitory activity, (iv) azadiraehtin derivative insecticides , (v) acaricidal combinations of neem seed extaet and bifenthrin, (vi) therapeutic compounds derived from the neem tree, and (vii) storage stable pesticide compositions comprising azadirachtin and epoxide. Of these, as many as 26 patents deal with neem-related substances being used as pest -control agen ts--as pesticides, insecticides, fungi-
KARKI : NEEM-I3ASED NATURAL PRODUCT ...... . 33
cid es or acaricid es. Corporate interest appears to be almost exclusively devoted to pest control.
Researchers seem to have looked for substances beyond azadirachtin-eith er derivat ive s of aza dirachtin, or extrac ts su bstantially free of it-to develop pest-control agents. But little progress appears to have been ach ieved on them beyond the work don e by th e Native Plant In stitute, USA (patent no 5,047, 242) .
Of the remainin g patents , two deal wi th therapeutic properties, of which on e was obtained by an individual inventor of USA on ph arma products and another by CSIR on a compound useful for controlling gastric hyperacidi ty and gastric ulceration. Th e only patent for neem's anti-fertility properties has been obtained by th e Nation al Institute of Immunology, New Delhi. Rohan and Haas Co has a patent for an edible oil extracted from neem seeds.
(b) Production Methods
In this fi eld, th e patents have been taken mainly for preparing azadirachtin , neem seed extracts and neem bark extract, and preparation of neem oil. Most of th ese patents deal with manufacturin g processes; esp ec ially tho se inv e ntion s whi c h h e lp increase storage stability, essential for enhancing shelf life and marketabili ty. Other patents deal with processes, which try to increase th e concentration of azadirachtin in th e final composition, remove conta minants like aflatoxin , and with ti ssue culture methods to produce azadirachtin in the laboratOI]'.
During 1996-2000, 14 patents have been granted in this category, most of th em are held by US corporation s. A few examples of such patents are: (i) process for preparing
purified azadirachtin in powder form from neem seeds and storage s tabl e aqu eous composition containing azadirachtin, (ii) method for producing azadirachtin by cell culture ofAzadirachta indica, (ii) method for producing azad irachtin concentrates from neem seed materials, (iii) preparation of high purity neem seed extracts, (iv) preparation of edible neem oil, and (v) method to prepare an improved storage stable neem seed extract.
(c) Extraction and Isolation Methods
Patents in this category are eith er on isolation of active principles or on extraction of azadirachlin and neem oil. There are three patents in this group during 1996-2000. Afew examples of such patents are: (i) process for th e isolation of an active prin cipl e from Azadirachta indica useful for controlling gastric hyperacidity and gastric ulceration, and (ii) co-extraction of azadirachtin ' and neem oil.
Analysis of patents fil ed or granted in India shows, more or less, th e same research trends. In fact, a few are common in both the groups. Patents falling und er extraction and isolation methods are five, more than th e US patents of th is group. Patents dealing with manufacturing processes are only three; the products obtain ed throug h th em are expected to be useful as insecticide/pesticide. The Hindustan Liver Ltd has obtain ed three Indian patents for upgrading the neem oil.
Results and Conclusion
The growing number of neem-related patents own ed by industrial firms / organizations, e specially in USA and India, is indicative of the tremendous inte rnational in terest in neem. While in USA, companies play predominant role in accelerating th e pace of th e technological developments in
34 J INTELLEC PROP RIGHTS,JANUARY 2001
the area of neem, in India the active role is played by CSIR in patenting in USA as well as in India. The US corporations have shown a consistent interest with a few patents appearing every year during 1990s. Indian inventors have taken a sizable number of US patents in the second half of this decade. Patents dealing with applications of neem products are more than patents on manufacturing processes. A vast majority of patents on neem taken in recent years relate to its use as a pesticide. Corporate interest appears to be almost exclusively devoted to pest-control. Among the patents dealing with manufacturing processes, majority of inventions are those which help increase the storage stability. Other patents deal with processes which try to increase the concentration of azadirachtin in the final composition. Most of the patents are on azadirachtin. Improvements in the purity of azadirachtin extract seem to be a challenge to the concerned scientific community of the world. Another challenging problem appears to be the stabilization of this chemical that becomes degraded after a few days. Indian
patents are more on the isolation and extraction methods.
References
1 The Neem Tree, http://www.neemtree.com/
2 Wealth of India CDROM Database (National Institute of Science Commu nication, New Delhi) 2000
3 Neem-A Tree for Solving Global Problems (National Academy Press, Washington, DC) 1992
4 Neem Foundation, http:/ /www.neemfoundation .org/patents.htm
5 Agrawal A, What'sinaneem? Down To Earth, 4(20) 1996,27-38.
6 Rajan TPS, Can a tree be patented? Chemical Weekly, 41 (10) 1995, 62
7 Indian patents: Materials from plant resources, Journal 0/ Intellectual Property Rights, 1 (1) 1996, 16-54
8 USPTO Web Patent Databases, http://patents.uspto.gov/
KARKI : NEEM-BASED NATURAL PRODUCT ...... . 35
Annexure 1- Applications for Indian patents
Patent App.No Date Patent Title Inventor
668/Mas/93 23.9.93 A combination of hydroponicum Dalmia Cantre for and a spray to improve the Biotechnology survival of tissue cultured plants with specific references to N eem
757/ De1/93 20.7.93 Preparation of edible Neem oil Rohm and Haas Co.
758/De1/93 20.7.93 Stable extract from neem oi Rohm and Haas Co
759/De1/93 20.7.93 Preparation of neem seed extract Rohm and haas Co.
1270,1271.1272 12.11.93 A process for preparation of National Research & 1273/De1/93 spermicidal agent from neem oil Development
or extractives Corporation
7/Mas/94 7-1-94 A method for preparing ayurvedic antivirus compound comprising three oils mainly neem seed oil.. Girivas Vishwanath Seth
9/Mas/94 10-1-94 Nimbecidine - Vegetable nil T. Stanes and Company including neem oil. enriched Ltd . with azadirachtin and the same extracted from neem seed and other parts of neem.
1397/DeI/93 9.12.93 A method for producing Rohm and Haas Co. azadirachtin
36 J INTELLEC PROP RIGHTS, JANUARY 2001
Annexure 2-US patents on neem-related processes and products"" -- contd
1. 5,900,493 Triterpene derivatives of azadirachtin having insect antifeedant and g rowth inhibitory activity
2 5,85,856,526 Pesticidal dry powder fo rmulation enrich ed in azadirachtin up to 88% an an emulsifiable concentTate enriched up to 30% of azad irachtin and a process process fo r preparing such fo rmulation and concentrate from neem seed/kernel
3 5,827,521 Shelf stable insect repellent, in sect growth regulator and in secticidal fo rmulations prepared from technical azadirachtin isolated from th e kern el extract of Azadirachta indica
4. 5,756,773 Triterpene derivatives of azad irachti n having insect antifeedant an d growth inhibitory activity
5. 5,736,145 Process for preparing purified azadirachtin in powd er form from neem seeds and storage stable aqueous composition containi ng azadirach tin
6. 5,730,986 Process for the isolation of an active principle fro m Azadirachta indica useful for controlling gastric hyperacidity and gastric ulceration
7. 5,698,423 Method for producing azadi rachtin by cell culture of Azadirachta indica
8. 5,695,763 Method for th e production of storage stable azadirachtin from seed kern els of the neem tree
9. 5,679,662 Synergistic use of azad irachtin and pyrethrum
10. 5,663,374 Triterpene derivatives of azadi rachtin having in sect antifeedant and growth inhibitory activi ty and a process fo r extracting such compounds fro m th e neem plant
11. 5,635,193 Stability of azadirachtin-containing solid
12. 5,626,848 Reduced-cloud-point clarified neem oil and methods of producing
13. 5,602,261 Triterpene derivatives of azadirachti n having in sect antifeedant an d growth inhibitory activity and a process for extracting such compounds from the neem plant
14. Hl,541 Method for producing azadirachtin concentrates from neem seed materials
15. 5,503,837 Co-extraction of azadirachtin and neem oil
16. 5,501,855 Neem oil as a male contraceptive
17. 5,472,700 Combinations of neem seed extract and bifenthrin for control of ectoparasites on animals
18. 5,420,318 Preparation of high purity neem seed extracts
19. 5,411,736 Hydrophic extracted neem oil-a novel insecticide
20. 5,409,708 Fungicidal compositions derived from neem oil and neem wax fractions
21. 5,405,612 Hydrophobic extracted neem oil-a novel insecticide
Contd
KARKl : NEEM-I3ASED NATURAL PRODUCT ...... . 37
Annexure 2-US patents on neem-related processes and products* - contd
22. 5,397,571 Co-extraction of azadirachtin and neem oil
23 . 5,395,951 Triterpene derivatives of azadirachtin having insect antifeedant and growth inhibitory activity and a process for extracting such compounds from the neem plant
24. 5,391,779 Stable extracts from neem seeds
26. 5,372,817 Insecticidal compositions derived from neem oil and neem wax fractions
26. 5,371,254 Preparation of edible neem oil
27. 5,370,873 Therapeutic compounds derived from the neem tree
28. 5,368,856 Hydrophobic extracted neem oil-a novel fungicide use
29. 5,356,628 Hydrophobic extracted neem oil-a novel fungicide
30. 5,352,697 Storage stable pesticide compositions comprising azadirachtin and epoxide
3l. 5,352,672 Acaricidal combinations of neem seed extract and bifenthrin
32. 5,298,251 Fungicide compositions derived from neem oil and neem wax fractions
33. 5,298,247 Neem oil fatty acid distillation residue based pesticide
34. 5,281,618 Storage stable high azadirachtin solution
35. 5,229,007 Selective removal of aflatoxin from azadirachtin containing compositions
36. 5,124,349 Storage stable azadirachtin formulation
37. 5,110,591 Neem oil emulsifier
38. 5,047,242 Azadirachtin derivative insecticides
39. 5,001,149 Azadirachtin derivative insecticides99
40. 5,001,146 Storage stable azadirachtin formulation
4l. 4,946,681 Method to prepare an improved storage stable neem seed extract
42. 4,943,434 Insecticidal hydrogenated neem extracts
43. 4,902,713 Azadirachtin-like compounds and insect-destroying agents containing them
44. 4,556,562 Stable anti-pest neem seed extract
45. 4,537,774 Hot-water extracts of neem bark
46. 4,515,785 Neem bark extracts
*Only those patents which carry in their titles keywords like neem or azadirachtin or Azadirachta indica or neem oil